Selection of anti-angiogenic bioactive principles of Oroxylum indicum against non-small cell lung cancer (NSCLC) - angiogenesis targets: A combinatorial in-silico approach

Lung cancer is among the most frequently diagnosed cancer type according to current epidemiological data sources. The NSCLC subtype comprises roughly 85% of all lung cancer cases. Tumor angiogenesis contributes to NSCLC proliferation and metastasis. Despite advancements in NSCLC treatment, challenges such as metastasis, relapse, and drug resistance persist, highlighting the urgent need for multi-target treatment strategies. This study applied a systematic in silico network pharmacology approach to check the effect of bioactive compounds from Oroxylum indicum ( O. indicum ) on possible key angiogenesis pathway regulators. Although several studies have reported the anticancer potential of O. indicum extracts, systematic identification of individual bioactive compounds and their molecular mechanisms remain limited. In this study, ligand- and disease-based databases were utilized to identify 208 common targets. PPI analysis, hub gene identification and literature-based screening shortlisted 10 targets (SRC, EGFR, JAK2, PTPN11, AKT1, HSP90AA1, PTK2, ERBB2, KDR (VEGFR-2), and CASP3). The bioactive compounds were screened and selected through ligand profiling, and a Compound-Target network was also constructed. GO and KEGG enrichment analyses revealed strong associations with critical cancer-related terms and pathways. Molecular docking revealed that Baicalein 6-O-glucoside exhibited comparatively stronger binding affinity to hub targets than controls, supported by molecular dynamics simulations and MM/GBSA analysis for EGFR and KDR (VEGFR-2) complexes. These findings present an opportunity for developing new therapeutic formulations against NSCLC.